This information is about a drug called gefitinib, which is commonly known as Iressa®. It is a man-made chemical that has been used in trials to treat lung cancer. Iressa was withdrawn as a treatment on the basis of the results of these trials, however newer data are looking more promising and it is making a comeback on the basis of a large Japanese study.
Developing a new drug
When a drug is being developed it has to go through various stages of research, called clinical trials. The aim of these is to find a safe dosage and find out what side effects the drug may cause. Trials can also show how effective a drug is, and whether it is better than the existing treatments, or has extra benefit when given alongside existing treatment.
Many drugs that are thought to be promising may be found not to be as good as existing treatments, or to have side effects that outweigh any benefits. For this reason, doctors and other medical staff carry out frequent and careful checks on the progress of each patient taking one of these developmental drugs.
If you are having a developmental drug, your doctor will explain all about the drug, the procedures being used, and how you will be looked after while you are taking it. If at any time you have concerns, you should ask your doctor or nurse for information and advice.
What is Iressa?
A number of different trials have used Iressa. Some of the early trials showed that it can shrink cancer tumours a little in some patients with advanced cancer (cancer which has already spread), who have had standard treatments for their particular type of cancer. Iressa also helped to improve symptoms for some people. However, the drug had no effect on some people in these trials.
Further trials were carried out to determine exactly how effective Iressa was and whether it helped to improve survival when compared to a placebo (an inactive drug). Unfortunately, the results of a large trial of nearly 1700 people with advanced lung cancer showed that Iressa did not help people to live any longer.
Newer data is more promising and it is making a comeback.
How it works
Iressa works by blocking (inhibiting) signals within the cancer cells, which prevents a series of chemical reactions that cause the cell to grow and divide. It is known as a signal transduction inhibitor. This process is described in detail below.
On the surface of many types of cancer cell are structures known as epidermal growth factor receptors (EGFRs). The receptors allow epidermal growth factor (a protein present in the body) to attach to them. When the epidermal growth factor (EGF) attaches to the receptor, it causes an enzyme called tyrosine kinase (TK) to trigger chemical processes inside the cell to make it grow and divide.
Iressa attaches itself to the EGF receptor on the cell and prevents the receptor from being activated. This stops the cells from dividing. Iressa therefore has the potential to stop the cancer cells from growing. It works in a different way from chemotherapy.
How it is given
Iressa is taken as a tablet once a day. The tablet should be taken at roughly the same time each day.
Possible side effects
Each person’s reaction to any drug is different. Some people have very few side effects, while others may experience more. We have outlined the most common side effects. These will not affect everyone taking Iressa. We have not included those side effects that are rare, and which are therefore unlikely to affect you. If you notice any effects that you think may be due to the drugs, but which are not listed below, please let your nurse or doctor know.
Diarrhoea
This can usually be easily controlled with medicine, but tell your doctor if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea.
Acne-like rash
Your skin may become dry, sore and itchy. Let your doctor know if you develop this side effect as they can prescribe medicines to help.
Loss of appetite
This is unusual, dietary advice can be given if necessary.
Feeling sick (nausea) and being sick (vomiting)
Let your doctor know if nausea is a problem as very effective anti-sickness medication can be prescribed.
Tiredness
Some people get tired while taking Iressa.
Eye problems
If you notice any change to your vision, or pain or redness of your eyes, let your doctor know.
Change in blood pressure
Iressa may make your blood pressure rise, especially if you already have high blood pressure. Tell your doctor if you get any headaches, dizziness or blurred vision.
Breathing problems
A rare side effect of gefitinib is inflammation of the lungs. If you become breathless or your breathing worsens, tell your doctor straight away. Although this is a rare side effect it is potentially very serious, and a small number of people have died because of the lung problems they have developed while taking Iressa. If you are worried about this potential side effect talk to your doctor or nurse.
Additional information
Keep the tablets in a safe place where children cannot reach them, as Iressa could harm them.
Iressa may interact with grapefruit juice. It is advisable not to drink it while you are having Iressa treatment.
If your doctor decides to stop the treatment, return any remaining tablets to the pharmacist. Do not flush them down the toilet or throw them away.
If you are sick just after taking the tablet, tell your doctor, as you may need to take another one.
If you forget to take a tablet, you can take it as soon as you remember, as long as it is more than 12 hours before your next scheduled dose. If it is less than 12 hours, do not take the missed dose.
Iressa may interact with other medicines. Let your doctor know about any medications you are taking, including any non-prescribed drugs such as complementary herbal therapies.
It is not advisable to become pregnant or father a child while having this treatment, as the developing foetus may be harmed. It is important to use effective contraception.
Additional Information For Healthcare Professionals
ADVERSE REACTIONS SIGNIFICANT
>10%:
- Dermatologic: Rash (43% to 54%), acne (25% to 33%), dry skin (13% to 26%)
- Gastrointestinal: Diarrhea (48% to 76%), nausea (13% to 18%), vomiting (9% to 12%)
1% to 10%:
- Cardiovascular: Peripheral edema (2%)
- Dermatologic: Pruritus (8% to 9%)
- Gastrointestinal: Anorexia (7% to 10%), weight loss (3% to 5%), mouth ulceration (1%)
- Neuromuscular & skeletal: Weakness (4% to 6%)
- Ocular: Amblyopia (2%), conjunctivitis (1%)
- Respiratory: Dyspnea (2%), interstitial lung disease (1% to 2%)
<1%:
Aberrant eyelash growth, angioedema, corneal erosion and membrane sloughing, epistaxis, erythema multiforme, eye pain, hematuria, hemorrhage, ocular hemorrhaging, ocular ischemia, pancreatitis, toxic epidermal necrolysis, urticaria
MECHANISM OF ACTION
The mechanism of antineoplastic action is not fully understood. Gefitinib inhibits tyrosine kinases (TK) associated with transmembrane cell surface receptors found on both normal and cancer cells. One such receptor is epidermal growth factor receptor. TK activity appears to be vitally important to cell proliferation and survival.
PHARMACODYNAMICS / KINETICS
- Absorption: Oral: slow
- Distribution: I.V.: 1400 L
- Protein binding: 90%, albumin and alpha1-acid glycoprotein
- Metabolism: Hepatic, primarily via CYP3A4; forms metabolites
- Bioavailability: 60%
- Half-life elimination: I.V.: 48 hours
- Time to peak, plasma: Oral: 3-7 hours
- Excretion: Faeces (86%); urine (<4%)